The Dangerous Rise of Antibiotic Resistance in Contemporary Spain

Connecticut College Digital Commons @ Connecticut College Toor Cummings Center for International Studies CISLA Senior Integrative Projects and the Liberal Arts (CISLA) 2020 The Dangerous Rise of Antibiotic Resistance in Contemporary Spain Isis Torrez Connecticut College Follow this and additional works at: https://digitalcommons.conncoll.edu/sip Recommended Citation Torrez, Isis, "The Dangerous Rise of Antibiotic Resistance in Contemporary Spain" (2020). CISLA Senior Integrative Projects. 18. https://digitalcommons.conncoll.edu/sip/18 This Honors Paper is brought to you for free and open access by the Toor Cummings Center for International Studies and the Liberal Arts (CISLA) at Digital Commons @ Connecticut College. It has been accepted for inclusion in CISLA Senior Integrative Projects by an authorized administrator of Digital Commons @ Connecticut College. For more information, please contact [email protected]. The views expressed in this paper are solely those of the author. The Misuse and Overuse of Antibiotics: The Cause of Antibiotic Resistant Bacteria Isis Torres-Nuñez Senior Integrated Project Advisor: Professor Bernhard Fall 2019 Connecticut College Torres-Nuñez 1 Abstract Antibiotic resistance is a global health threat that has jeopardized the worth of antibiotics, which have previously transformed medicine in the past decades by saving millions of lives. With thousands of people now dying yearly as a result of bacteria being resistant to antibiotics, we are in great need of new antibiotics. However, it is our careless overuse and misuse of the ones we already have that has resulted in this global health crisis. Thus, multidisciplinary approaches need to be made across the globe, in health care settings, and in agriculture to diminish our abuse of antibiotics so that when we do discover new ones, we are not presented with this problem once more. Bacteria in the Human Body Of all microorganisms and living creatures on earth, bacteria are the most abundant, inhabiting soils, oceans, and even human bodies. In ecosystems, these organisms play key roles in cycling essential nutrients such as carbon, hydrogen, oxygen, and nitrogen. In human bodies, they help metabolize food, provide essential nutrients, periodically fight off invading pathogens, and much more. For example, some bacteria in the intestinal wall play a vital role in fighting infection by producing bacteriocins, which are small proteins that prevent harmful microorganisms from growing (Gorbach 1996). Other bacteria in the human gastrointestinal tract are responsible for synthesizing vitamin K2, an essential component of an enzyme necessary for blood clotting (Berkner 2000). Even more interesting, some studies have proven that changing the bacteria in the gastrointestinal tract has even been associated with cancer (Motevaseli et al. 2017). Thus, as you can see, not all bacteria are harmful and human bodies rely heavily on many Torres-Nuñez 2 of them for survival. Unfortunately, however, some bacteria are toxic, these are known as pathogenic bacteria. Pathogenic bacteria can give rise to an array of infections all over the body, ranging from skin and hair to blood and internal organs. These organisms typically cause infection through the release of harmful toxins and can spread it to others through direct contact, contaminated food and water, bodily fluids, and/or airborne transmission (Drexler 2010). What makes them all the more dangerous is their ability to rapidly reproduce and acquire new genetic material, such as genes that code for antibiotic resistance, from surrounding bacteria (Holmes 1996). Through these methods, bacteria are able to incorporate foreign DNA into their genome, creating recombinant DNA and allowing them to express those foreign genes permanently (Holmes 1996). As a result, bacteria are able to rapidly adapt to their environments and survive even in the presence of toxins such as antibiotics. Antibiotics Antibiotics are a type of drugs that fight bacterial infections through many different mechanisms (Table 1). Since bacteria (which are unicellular) and human cells share similarities in their structure, antibiotics are designed to be specific enough that human cells don’t get harmed in the process of eradicating infections. For example, penicillins work by inhibiting the cross linking of bacterial cell walls, a structure that human cells lack, in order to cause disintegration (Strominger et al. 1971). In contrast, tetracyclines work by preventing the binding of an important RNA molecule (known as aminoacyl tRNA) to ribosomes, which are the organelles that synthesize proteins (Chopra and Roberts 2001). Even though protein synthesis is Torres-Nuñez 3 also carried out by human cells, humans use different ribosomes than bacteria. While bacteria use ribosomes composed of 50s large subunits and 30s small subunits, humans use ribosomes composed of 60S large subunits and 40s small subunits (Berg et al. 2002). Thus, allowing tetracyclines to target bacterial protein synthesis specifically and not human protein synthesis. Even though different classes of antibiotics target bacteria through distinct and specific approaches (Table 1), they all generally act as bacteriostatic agents to restrict cell growth/reproduction or as bactericidal agents to straightforwardly cause cell death (Ocampo et al. 2014). The range of side effects that patients experience as a result of these drugs perhaps is due to the drug mechanism of action. For example, accidentally targeting a human ribosome instead of a bacterial ribosome by tetracyclines might lead to unwanted symptoms. Other factors include the concentration of antibiotics used and the percent of healthy, pathogen-fighting bacteria that are accidentally killed in the process of fighting an infection. Consequently, the more that bacteria are exposed to antibiotics (and survive), the less sensitive they become to them, requiring higher concentrations of antibiotics to be prescribed (Zaman et al. 2017). This in turn results in unwanted effects, one of the biggest ones being antibiotic resistance. Table 1. Common Antibiotics and Their Modes of Action Class of Examples Mechanism of Action Antibiotic β-Lactams Penicillins (penicillin G, Enter the bacterial cell through porins and methicillin, amoxicillin), permanently acylate penicillin binding proteins (PBPs) which catalyze the Cephalosporins formation of peptidoglycan in cell wall. (cephalothin, cephalexin) Additionally, can bind to the active site of transpeptidase to inhibit the cross-linking Carbapenems (Imipenem, of peptidoglycan, resulting in cell lysis. meropenem) Torres-Nuñez 4 Tetracyclines Tetracycline, doxycycline, Inhibit protein synthesis by preventing the clomocycline attachment of aminoacyl-tRNA to ribosomal acceptor (A) site. Quinolones Ciprofloxacin, Harm DNA by increasing the concentration temafloxacin of enzyme-DNA cleavage complexes, such as topoisomerase IV and gyrase. MLS Family Macrolides (erythromycin, Inhibit protein synthesis by binding to the azithromycin) large ribosomal subunit, near the peptidyl transferase center. Some inhibit the Lincosamides (lincomycin, peptidyl transferase reaction, others block clindamycin) the exit of peptidyl tRNAs which results in premature dissociation. Streptogramin (virginiamycin, pristinamycin) Sulfonamides Sulphanilamide, Act as competitive antagonists to sulfathalidine para-aminobenzoic acid, a precursor to folic acid) and necessary for nucleic acid synthesis. Glycopeptides Vancomycin, telavancin Form stable complexes, through hydrogen bonding, with clefts in bacterial cell walls which inhibit the formation of the glycan chain backbone. Aminoglycosides Streptomycin, kanamycin Interfere with protein synthesis by either binding to the small 30s subunit or by incorporating incorrect amino acids into the growing chain. Causes of Antibiotic Resistance on a Cellular Level Due to natural selection and evolution, all living organisms develop mechanisms in order to survive as the conditions of their environment change and become challenging. Just as humans have developed antibiotics to fight bacterial infections, bacteria have developed mechanisms to fight off those same toxins trying to kill them. The two major ways in which bacteria can develop antibiotic resistance are intrinsically or with acquirance (Hawkey 1998). With intrinsic Torres-Nuñez 5 resistance, the event is random and naturally occurring in an effort to adapt to environmental stressors and pressures. These mutations are often spontaneous and their origins tend to be obscure since they result from years of evolution (Hawkey 1998). With acquired resistance, the bacteria develop resistance after being sensitized to antibiotics or after obtaining new DNA. New DNA can be obtained through a process called horizontal gene transfer (HGT) in which genetic material is swapped between neighboring bacteria through transformation, transduction, or conjugation (Clark and Pazdernik 2013). With transformation, bacteria take up extracellular DNA from their surroundings. With transduction, bacteria are infected with bacteriophages (viruses) that carry donor DNA. With conjugation, donor bacteria transfer their DNA to recipient bacteria through mating. With either of these three methods, HGT allows bacteria to transfer DNA across all different types of bacteria, even with ones that are not of the same species. This is one of the factors that makes the spread of antibiotic resistance occur rapidly and easily. The newly obtained DNA

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